Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 50, Issue 8, Pages 1993-1997Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm061477+
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Funding
- NHLBI NIH HHS [HL081655, R01 HL081655] Funding Source: Medline
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A series of phenolic hydrazones were synthesized and evaluated for their inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity. Compound 7 emerged as a potent inhibitor of MIF with an IC50 of 130 nM. Compound 7 dose-dependently suppressed TNF alpha secretion from lipopolysaccharide stimulated macrophages. The therapeutic importance of the MIF inhibition by 7 is demonstrated by the significant protection from the lethality of sepsis when administration of the compound was initiated in a clinically relevant time frame.
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